seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   1 MTTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:cd15321    32 LTSRSLRAPQNLFLVSLAAADILVATLIIPFSLANELMGYWYFRKTWCEIYLALDVLFCTSSIVHLCAISLDRYWSVSRA 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15321   112 IEYNSKRTPRRIKCIILIVWLIAAVISLPPLIYKGKQKDEQGGLPQCKLNEEAWYILSSSIGSFFAPCLIMILVYLR 188

alpha-2 adrenergic receptors subtype B, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   1 MTTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:cd15321    32 LTSRSLRAPQNLFLVSLAAADILVATLIIPFSLANELMGYWYFRKTWCEIYLALDVLFCTSSIVHLCAISLDRYWSVSRA 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15321   112 IEYNSKRTPRRIKCIILIVWLIAAVISLPPLIYKGKQKDEQGGLPQCKLNEEAWYILSSSIGSFFAPCLIMILVYLR 188

G protein-coupled chemokine receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   6 LRAPQNLFLVSLAAADILVaTLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEYNS 85
Cdd:PHA03087   70 IKTPMDIYLLNLAVSDLLF-VMTLPFQIYYYILFQWSFGEFACKIVSGLYYIGFYNSMNFITVMSVDRYIAIVHPVKSNK 148

                          90       100
                  ....*....|....*....|....*..
gi 1918138064  86 KRTPRRIKCIILTVWLIAAIISLPPLI 112
Cdd:PHA03087  149 INTVKYGYIVSLVIWIISIIETTPILF 175

alpha-2 adrenergic receptors subtype B, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   1 MTTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:cd15321    32 LTSRSLRAPQNLFLVSLAAADILVATLIIPFSLANELMGYWYFRKTWCEIYLALDVLFCTSSIVHLCAISLDRYWSVSRA 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15321   112 IEYNSKRTPRRIKCIILIVWLIAAVISLPPLIYKGKQKDEQGGLPQCKLNEEAWYILSSSIGSFFAPCLIMILVYLR 188

alpha-2 adrenergic receptors subtype C, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   1 MTTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:cd15323    26 LTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMGYWYFGQVWCNIYLALDVLFCTSSIVHLCAISLDRYWSVTQA 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIyKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15323   106 VEYNLKRTPRRVKAIIVTVWLISAVISFPPLI-SMYRDPEGDVYPQCKLNDETWYILSSCIGSFFAPCLIMILVYIR 181

alpha-2 adrenergic receptors subtype D, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   1 MTTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:cd15324    26 FTSRALRAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGSTWCAFYLALDVLFCTSSIVHLCAISLDRYWSVTKA 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIYkgdqgpQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15324   106 VSYNLKRTPKRIKRMIAVVWVISAVISFPPLLM------TKHDEWECLLNDETWYILSSCTVSFFAPGLIMILVYCK 176

serotonin receptor subtypes 1, 5 and 7, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes serotonin receptor subtypes 1, 5, and 7 that are activated by the neurotransmitter serotonin. The 5-HT1 and 5-HT5 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family. The 5-HT1 receptor subfamily includes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as 5-HT2C receptor. The 5-HT5A and 5-HT5B receptors have been cloned from rat and mouse, but only the 5-HT5A isoform has been identified in human because of the presence of premature stop codons in the human 5-HT5B gene, which prevents a functional receptor from being expressed. The 5-HT7 receptor is coupled to Gs, which positively stimulates adenylate cyclase activity, leading to increased intracellular cAMP formation and calcium influx. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   2 TTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRAL 81
Cdd:cd15064    27 LTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTGRWILGQVLCDIWISLDVTCCTASILHLCVIALDRYWAITDAV 106

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1918138064  82 EYNSKRTPRRIKCIILTVWLIAAIISLPPLIykGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15064   107 EYAHKRTPKRAAVMIALVWTLSICISLPPLF--GWRTPDSEDPSECLISQDIGYTIFSTFGAFYIPLLLMLILYWK 180

tyramine/octopamine receptor-like, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine/octopamine receptors and similar proteins found in insects and other invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   1 MTTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:cd15060    26 FTYRPLRIVQNFFIVSLAVADLAVAIFVLPLNVAYFLLGKWLFGIHLCQMWLTCDILCCTASILNLCAIALDRYWAIHDP 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15060   106 INYAQKRTLKRVLLMIVVVWALSALISVPPLIGWNDWPENFTETTPCTLTEEKGYVIYSSSGSFFIPLLIMTIVYVK 182

dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled dopamine 1-like receptor 2 is expressed in Drosophila heads and it shows significant sequence similarity with vertebrate and invertebrate dopamine receptors. Although the Drosophila Dop1R2 receptor does not cluster into the D1-like structural group, it does show pharmacological properties similar to D1-like receptors. As shown in vertebrate D1-like receptors, agonist stimulation of Dop1R2 activates adenylyl cyclase to increase cAMP levels and also generates a calcium signal through stimulation of phospholipase C.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   4 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLG-YWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 82
Cdd:cd15067    28 RYLRTVTNYFIVSLAVADLLVGSIVMPFSILHEMTGgYWLFGRDWCDVWHSFDVLASTASILNLCVISLDRYWAITDPIS 107

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1918138064  83 YNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15067   108 YPSRMTKRRALIMIALVWICSALISFPAIAWWRAVDPGPSPPNQCLFTDDSGYLIFSSCVSFYIPLVVMLFTYYR 182

tyramine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine-specific receptors and similar proteins found in insects and other invertebrates. These tyramine receptors form a distinct receptor family that is phylogenetically different from the other tyramine/octopamine receptors which also found in invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   2 TTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRAL 81
Cdd:cd15061    26 TTRRLRTITNCYIVSLATADLLVGVLVLPLAIIRQLLGYWPLGSHLCDFWISLDVLLCTASILNLCCISLDRYFAITYPL 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1918138064  82 EYNSKRTPRRIKCIILTVWLIAAIISLPPLIykGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15061   106 KYRTKRSRRLAITMILAVWVISLLITSPPLV--GPSWHGRRGLGSCYYTYDKGYRIYSSMGSFFLPLLLMLFVYLR 179

D2-like dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. In contrast, activation of D2-like family receptors is linked to G proteins of the G(i) family, which inhibit adenylate cyclase. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   4 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELL-GYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 82
Cdd:cd15053    29 RSLQTATNYFIVSLAVADLLVAILVMPFAVYVEVNgGKWYLGPILCDIYIAMDVMCSTASIFNLCAISIDRYIAVTQPIK 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1918138064  83 YNSKRTPRRIKCIILTVWLIAAIISLPPLIykGDQGPQTHERPQCKLnQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15053   109 YARQKNSKRVLLTIAIVWVVSAAIACPLLF--GLNNVPYRDPEECRF-YNPDFIIYSSISSFYIPCIVMLLLYYR 180

serotonin receptor subtype 1A from invertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   4 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRaLEY 83
Cdd:cd15331    29 RSLQGVSNYLILSLAVADLMVAVLVMPLSAVYEVSQHWFLGPEVCDMWISMDVLCCTASILHLVAIALDRYWAVTN-IDY 107

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1918138064  84 NSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQG--PQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15331   108 IRRRTAKRILIMIAVVWFVSLIISIAPLFGWKDEDdlDRVLKTGVCLISQDYGYTIFSTVGAFYVPLLLMIIIYWK 183

serotonin receptor subtype 1A from vertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   4 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 83
Cdd:cd15330    29 RSLQNVANYLIGSLAVTDLMVSVLVLPMAALYQVLNKWTLGQVTCDLFIALDVLCCTSSILHLCAIALDRYWAITDPIDY 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1918138064  84 NSKRTPRRIKCIILTVWLIAAIISLPPLIykGDQGPQTHERPQ-CKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15330   109 VNKRTPRRAAVLISLTWLIGFSISIPPML--GWRTPEDRSDPDaCTISKDPGYTIYSTFGAFYIPLILMLVLYGR 181

7 transmembrane receptor (rhodopsin family); This family contains, amongst other G-protein-coupled receptors (GCPRs), members of the opsin family, which have been considered to be typical members of the rhodopsin superfamily. They share several motifs, mainly the seven transmembrane helices, GCPRs of the rhodopsin superfamily. All opsins bind a chromophore, such as 11-cis-retinal. The function of most opsins other than the photoisomerases is split into two steps: light absorption and G-protein activation. Photoisomerases, on the other hand, are not coupled to G-proteins - they are thought to generate and supply the chromophore that is used by visual opsins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   2 TTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELL-GYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRA 80
Cdd:pfam00001  11 RNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNhGDWPFGSALCKIVGALFVVNGYASILLLTAISIDRYLAIVHP 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064  81 LEYNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQC------KLNQEAWYILASSIGSFFAPCLIMILV 154
Cdd:pfam00001  91 LRYKRRRTPRRAKVLILVIWVLALLLSLPPLLFGWTLTVPEGNVTVCfidfpeDLSKPVSYTLLISVLGFLLPLLVILVC 170

                  ...
gi 1918138064 155 YLR 157
Cdd:pfam00001 171 YTL 173

serotonin receptor subtypes 1B and 1D, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   3 TRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 82
Cdd:cd15333    32 TRKLHTPANYLIASLAVTDLLVSILVMPISIVYTVTGTWTLGQVVCDIWLSSDITCCTASILHLCVIALDRYWAITDAVE 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1918138064  83 YNSKRTPRRIKCIILTVWLIAAIISLPPLIYKgdQGPQTHERPQCKLNQE-AWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15333   112 YSKKRTPKRAAVMIALVWVISISISLPPFFWR--QAKAEEEVSECVVNTDhILYTVYSTVGAFYIPTLLLIALYGR 185

serotonin receptor subtype 2, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   4 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLG-YWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 82
Cdd:cd15052    29 KRLQNVTNYFLMSLAIADLLVGLLVMPLSILTELFGgVWPLPLVLCLLWVTLDVLFCTASIMHLCTISLDRYMAIRYPLR 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1918138064  83 YNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQGPQTHERPQCKLNQEAwYILASSIGSFFAPCLIMILVY 155
Cdd:cd15052   109 TRRNKSRTTVFLKIAIVWLISIGISSPIPVLGIIDTTNVLNNGTCVLFNPN-FVIYGSIVAFFIPLLIMVVTY 180

beta adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta adrenergic receptor (beta adrenoceptor), also known as beta AR, is activated by hormone adrenaline (epinephrine) and plays important roles in regulating cardiac function and heart rate, as well as pulmonary physiology. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of beta-ARs can lead to cardiac dysfunction such as arrhythmias or heart failure. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   3 TRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 82
Cdd:cd15058    28 TSRLQTMTNIFITSLACADLVMGLLVVPLGATIVVTGKWQLGNFWCELWTSVDVLCVTASIETLCVIAVDRYIAITRPLR 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064  83 YNSKRTPRRIKCIILTVWLIAAIISLPPLI---YKGD--QGPQTHERPQC---KLNQEawYILASSIGSFFAPCLIMILV 154
Cdd:cd15058   108 YQVLLTKRRARVIVCVVWIVSALVSFVPIMnqwWRANdpEANDCYQDPTCcdfRTNMA--YAIASSVVSFYIPLLIMIFV 185

                  ...
gi 1918138064 155 YLR 157
Cdd:cd15058   186 YAR 188

serotonin receptor subtype 1E, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   2 TTRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRAL 81
Cdd:cd15335    27 TTKKLHQPANYLICSLAVTDFLVAVLVMPLSITYIVMDTWTLGYFICEIWLSVDMTCCTCSILHLCVIALDRYWAITDAI 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064  82 EYNSKRTPRRIKCIILTVWLIAAIISLPPLIYKGDQ---GPQtherpQCKLNQE-AWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15335   107 EYARKRTAKRAGLMILTVWTISIFISIPPLFWRNHHdanIPS-----QCIIQHDhVIYTIYSTFGAFYIPLTLILILYYR 181

serotonin receptor subtype 5, member of the class A family of seven-transmembrane G protein-coupled receptors; 5-HT5 receptor, one of 14 mammalian 5-HT receptors, is activated by the neurotransmitter and peripheral signal mediator serotonin (also known as 5-hydroxytryptamine or 5-HT). The 5-HT5A and 5-HT5B receptors have been cloned from rat and mouse, but only the 5-HT5A isoform has been identified in human because of the presence of premature stop codons in the human 5-HT5B gene, which prevents a functional receptor from being expressed. 5-HT5 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/0) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   7 RAPQNLfLVSLAAADILVATLIIPFSLANELLGY-WYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEYnS 85
Cdd:cd15328    33 RVPHNL-VASMAVSDVLVAALVMPLSLVHELSGRrWQLGRSLCQVWISFDVLCCTASIWNVTAIALDRYWSITRHLEY-T 110

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1918138064  86 KRTPRRIKCI-ILTVWLIAAIISLPPLIYkGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVY 155
Cdd:cd15328   111 LRTRRRISNVmIALTWALSAVISLAPLLF-GWGETYSEDSEECQVSQEPSYTVFSTFGAFYLPLCVVLFVY 180

beta-1 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta-1 adrenergic receptor (beta-1 adrenoceptor), also known as beta-1 AR, is activated by adrenaline (epinephrine) and plays important roles in regulating cardiac function and heart rate. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of betrayers can lead to cardiac dysfunction such as arrhythmias or heart failure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   3 TRSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 82
Cdd:cd15958    28 TQRLQTLTNLFITSLACADLVMGLLVVPFGATLVVRGRWLYGSFFCELWTSVDVLCVTASIETLCVIAIDRYLAITSPFR 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064  83 YNSKRTPRRIKCIILTVWLIAAIISLPPLIY-----KGDQGPQTHERPQ-CKLNQEAWYILASSIGSFFAPCLIMILVYL 156
Cdd:cd15958   108 YQSLLTRARAKGIVCTVWAISALVSFLPIMMhwwrdEDDQALKCYEDPGcCDFVTNRAYAIASSIISFYIPLLIMIFVYL 187

                  .
gi 1918138064 157 R 157
Cdd:cd15958   188 R 188

beta-2 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; Beta-2 AR is activated by adrenaline that plays important roles in cardiac function and pulmonary physiology. While beta-1 AR and beta-2 AR are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway, beta-2 AR can couple to both G(s) and G(i) proteins in the heart. Moreover, beta-2 AR activation leads to smooth muscle relaxation and bronchodilation in the lung. The beta adrenergic receptors are a subfamily of the class A rhodopsin-like G protein-coupled receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   6 LRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEYNS 85
Cdd:cd15957    31 LQTVTNYFITSLACADLVMGLAVVPFGAAHILLKTWTFGNFWCEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQS 110

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1918138064  86 KRTPRRIKCIILTVWLIAAIISLPPLI---YKGDQGPQTH---ERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15957   111 LLTKNKARVIILMVWIVSGLTSFLPIQmhwYRATHQEAINcyaEETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSR 188

trace amine-associated receptor 1 and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptor 1 (TAAR1) is one of the 15 identified trace amine-associated receptor subtypes, which form a distinct subfamily within the class A G protein-coupled receptor family. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. TAAR1 is coupled to the Gs protein, which leads to activation of adenylate cyclase, and is thought to play functional role in the regulation of brain monoamines. TAAR1 is also shown to be activated by psychoactive compounds such as Ecstasy (MDMA), amphetamine and LSD. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1918138064   4 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 83
Cdd:cd15314    29 KQLHTPTNYLILSLAVADLLVGGLVMPPSMVRSVETCWYFGDLFCKIHSSFDITLCTASILNLCFISIDRYYAVCQPLLY 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1918138064  84 NSKRTPRRIKCIILTVWLIAAI----ISLPPLIYKGDQGPQTHERPQCKLNQEAWYILASSIGSFFAPCLIMILVYLR 157
Cdd:cd15314   109 RSKITVRVVLVMILISWSVSALvgfgIIFLELNIKGIYYNHVACEGGCLVFFSKVSSVVGSVFSFYIPAVIMLCIYLK 186